tbuckley/cabot-search huggingface dataset:
Antibody seroprevalence against SARS-Cov-2 among chronic myeloid leukemia patients.
Authors: Marisol Miranda, Danielle Bradshaw, Jaspreet Farmaha, Reeya Patel, Kimya Jones, Harmanpreet Singh, Ashutosh Vashisht, Nikhil Shri Sahajpal, Ravindra Kohle, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2022)

e19061 Background: The rapid spread of SARS-CoV-2 has elicited an equally rapid development of effective vaccines, leading to a reduction of COVID-19 severity and deaths. There is limited data on COVID-19-related immunity in chronic myeloid leukemia (CML) patients. Methods: SPARTA (SARS2 SeroPrevalence And Respiratory Tract Assessment) is an ongoing observational study for participants age ≥18 years to investigate immunity to SARS-CoV-2 after infection and/or vaccination. We included patients with CML and compared them with a non-cancer group. We collected saliva and peripheral blood to measure antigen levels by RT-PCR and antibodies (secretory IgG antibodies and neutralizing antibodies). Results: From October 1, 2021, to February 4, 2022, we prospectively enrolled 49 participants (23 CML, 26 non-cancer). Most were male (56.5%) in the CML group and female in the control group (61.5%), mean age 56.39 y vs. 51.96 y, respectively, and self-identified as white (87% vs. 76.9%). In the CML group, 11 (47.8%) had ≥1 comorbidities, vs 13 (50%) in the control group. Twenty-one (91.3%) CML patients were receiving tyrosine-kinase inhibitors; 4 (18.2%) non-cancer subjects reported taking any medication. Most participants in both groups had received at least one dose of COVID-19 vaccine (73.9% vs. 73.1%); 100% of CML patients received two doses vs. 84.2% of controls; the CML group had a higher percentage of subjects fully vaccinated (66.7% vs. 25%). The CML group had a lower percentage of patients previously diagnosed with COVID-19 (8.8% vs. 57.7%). However, there was no difference in the detection of SARS-CoV-2 antigen at the time of enrollment (0% vs. 4%). SARS-CoV-2 IgG antibodies were detected in most of the participants regardless of cancer status (78.3% in the CML cohort and 88% in the non-cancer cohort), and neutralizing antibodies were detected in 82.6% and 95.6%, respectively. The two groups had comparable IgG (mean 146.3 Ru/ml vs. 148.9 Ru/ml) and neutralizing (mean 1329.1 ng/ml vs. 1112 ng/ml) antibody levels. Conclusions: Our preliminary data comparing concomitant cohorts with similar socio-demographic characteristics and medical history indicate that a diagnosis of CML did not impact the development of antibodies against SARS-CoV-2. We are conducting continuous analysis of antibodies levels over time to assess the evolution of antibody immunity and functional studies including cellular immunity assessments.[Table: see text]
The impact of COVID-19 and armed conflict on cancer care in Armenia: A cross-sectional study.
Authors: Yeva Margaryan, Liana Hambardzumyan, Tigran Aghabekyan, Gregory Peter Kalemkerian, Samvel Danielyan, Armen Muradyan, Gevorg Tamamyan, Stella Arakelyan
Journal: Journal of Clinical Oncology (2022)

e18551 Background: The COVID-19 pandemic has interrupted the spectrum of cancer services, exposing vulnerable cancer patients to significant risks. In Armenia, the negative effect of the pandemic was amplified by the Nagorno-Karabakh war in September-November 2020. We explored the combined impact of the COVID-19 pandemic and armed conflict on cancer care provision in Yerevan, Armenia. Methods: We carried out a cross-sectional survey among all oncologists, nurses, and clinical residents (n = 123) actively providing cancer care to adults and children since 2019 at three publicly-funded institutions in Yerevan, Armenia, namely the National Center of Oncology, Hematology center after prof. R.H.Yeolyan, and Mikaelyan Institute of Surgery. Data collection was conducted between November 1 and December 27, 2021. The survey included 71 items assessing institutional characteristics, COVID-19 diagnoses, disruptions to care, adaptations of care, and availability of human and material resources. Descriptive statistics were used to analyze responses from 89 participants (72%). Results: Disruptions to cancer care during the COVID-19 pandemic were reported due to staff absenteeism (16%) and lack of access to cancer treatment [chemotherapy (14%), radiotherapy (7%), surgery (7%)], elective surgery (27%), intensive care services (10%), diagnostic examinations (3%), and inpatient beds (6%). Shortages of clinical staff for pediatric cancer care were noted by 40% of respondents and were mainly attributed to COVID-19 infection (53%) or self-isolation due to testing positive for COVID-19 (25%). Half of the respondents reported suboptimal cancer patient care and outcomes (e.g. delayed diagnosis and treatment, complications of treatment, elevated mortality rates) caused primarily by the de-prioritization of cancer services during the COVID-19 pandemic. The main issues reported by the respondents during the armed conflict were delays in elective surgery (36%) and staff shortages (17%). Confirmed cases of COVID-19 among patients were reported by respondents as: &lt; 10 (by 6% of respondents), 11-50 (36%), 51-100 (27%) and &gt; 100 (7%). Ten respondents (11%) reported that colleagues had died after contracting COVID-19. Twenty-six percent of respondents reported that the overall rate of hospitalizations decreased during the pandemic and 12% reported increased use of telemedicine. Reductions in material resources were reported by 18% of respondents, while 15% reported funding cuts to their unit by the institution. Conclusions: The COVID-19 pandemic and concurrent armed conflict led to disruptions in cancer care in Armenia, resulting in suboptimal care and outcomes for cancer patients. These findings emphasize the need for proactive planning to maintain standards of cancer care delivery in times of societal crises.
Error in Figure 1
Journal: JAMA Network Open (2022)

Stephen Salerno, MS; Joseph M. Messana, MD; Garrett W. Gremel, MS; Claudia Dahlerus, PhD; Richard A. Hirth, PhD; Peisong Han, PhD; Jonathan H. Segal, MD; Tao Xu, PhD; Dan Shaffer, MS; Amy Jiao, MA; Jeremiah Simon, MPH; Lan Tong, MA, MS; Karen Wisniewski, MPH; Tammie Nahra, PhD; Robin Padilla, MS; Kathryn Sleeman, MA; Tempie Shearon, MS; Sandra Callard, MHSA; Alexander Yaldo, BS; Lisa Borowicz, BS; Wilfred Agbenyikey, ScD, MPH; Golden M. Horton, MS; Jesse Roach, MD; Yi Li, PhD
Putative rhythms in attentional switching can be explained by aperiodic temporal structure
Authors: Geoffrey Brookshire
Journal: Nature Human Behaviour (2022)

Abstract The neural and perceptual effects of attention were traditionally assumed to be sustained over time, but recent work suggests that covert attention rhythmically switches between objects at 3–8 Hz. Here I use simulations to demonstrate that the analysis approaches commonly used to test for rhythmic oscillations generate false positives in the presence of aperiodic temporal structure. I then propose two alternative analyses that are better able to discriminate between periodic and aperiodic structure in time series. Finally, I apply these alternative analyses to published datasets and find no evidence for behavioural rhythms in attentional switching after accounting for aperiodic temporal structure. The techniques presented here will help clarify the periodic and aperiodic dynamics of perception and of cognition more broadly.
Risk of myocarditis and pericarditis after the COVID-19 mRNA vaccination in the USA: a cohort study in claims databases
Authors: Hui-Lee Wong, Mao Hu, Cindy Ke Zhou, Patricia C Lloyd, Kandace L Amend, Daniel C Beachler, Alex Secora, Cheryl N McMahill-Walraven, Yun Lu, Yue Wu, Rachel P Ogilvie, Christian Reich, Djeneba Audrey Djibo, Zhiruo Wan, John D Seeger, Sandia Akhtar, Yixin Jiao, Yoganand Chillarige, Rose Do, John Hornberger, Joyce Obidi, Richard Forshee, Azadeh Shoaibi, Steven A Anderson
Journal: The Lancet (2022)
Glioblastoma response to blood-brain-barrier permeable, MGMT-agnostic therapeutic LP-184 and sensitization by nucleotide-excision repair deficiency.
Authors: Joseph McDermott, Bachchu Lal, Hernando Lopez-Bertoni, Aditya Kulkarni, Jianli Zhou, Caleb Schimke, Umesh Kathad, Kishor Bhatia, Panna Sharma, John Laterra
Journal: Journal of Clinical Oncology (2022)

e14023 Background: Glioblastoma (GBM), a WHO Grade IV cancer, is the most common and most aggressive primary malignant brain tumor. Prognosis following best standard-of-care surgical resection, radiation and temozolomide (TMZ) chemotherapy is poor, with median overall survival 15-18 months. TMZ, which acts primarily by methylating DNA at O6-guanine, has marginal efficacy in ̃70% of patients due to tumor expression of O-6-methylguanine-DNA methyltransferase (MGMT) and there is no effective therapy at tumor recurrence. New treatment options are therefore desperately needed for GBM patients. LP-184 is an acylfulvene-derived prodrug that is activated by the oxidoreductase PTGR1 and primarily alkylates adenine at the N 3 -position. Bioinformatic analysis showed that PTGR1 is elevated in clinical GBM tumor samples compared to normal brain. LP-184 response is influenced by tumor DNA repair status, and acylfulvene-induced damage is mainly repaired by the transcription-coupled nucleotide-excision repair (TC-NER) pathway. Spironolactone, an FDA approved, blood-brain-barrier permeable diuretic, induces degradation of ERCC3 protein, a key TC-NER component. Response of NER-deficient GBM was tested through co-administration of LP-184 and spironolactone. Methods: Cell viability assays with exposure to LP-184, with and without spironolactone, were used to determine IC 50 values in vitro. Subcutaneous or intracranial tumor xenograft models were used to determine tumor volume or survival differences between control and LP-184 treated mice. Results: Nanomolar concentrations of LP-184 inhibited in vitro viability of multiple GBM cell models including 4 NCI-60 GBM cell lines (mean IC 50 = 286 nM), the TMZ-resistant LN-18 cell line (IC 50 = 46 nM), M1123 GBM neurosphere line (IC 50 = 151 nM), and a low passage GBM neurosphere isolate (IC 50 = 306 nM). Co-treatment with spironolactone resulted in a 3-6 fold decrease in LP-184 IC 50 values in M1123, Mayo39, and U87 cultures. Pharmacokinetic analyses in SCID mice following a single LP-184 infusion (4 mg/kg, i.v.) showed favorable CNS bioavailability with brain/plasma ratio 0.11 (C max = 839 nM) and brain tumor/plasma ratio 0.2 (C max = 2.53 µM). LP-184 (4mg/kg i.v., q.o.d X 4) induced complete regression of all pre-established s.c. U87 xenografts (N = 5) and 3 of 6 M1123 s.c. xenografts (mean tumor volumes: 1456 ± 349 mm 3 controls vs 84 ± 39 LP-184, p &lt; 0.001) and statistically significantly prolonged survival of mice bearing pre-established orthotopic U87 and M1123 xenografts (p &lt; 0.0001). Conclusions: These preclinical results establish LP-184 as a promising new agent for future clinical testing in patients with GBM and suggest that LP-184 may be particularly efficacious in patients with intrinsic or spironolactone-induced NER deficient tumors.
Difficult and complicated oral ulceration: an expert consensus guideline for diagnosis
Authors: Xin Zeng, Xin Jin, Liang Zhong, Gang Zhou, Ming Zhong, Wenmei Wang, Yuan Fan, Qing Liu, Xiangmin Qi, Xiaobing Guan, Zhimin Yan, Xuemin Shen, Yingfang Wu, Lijie Fan, Zhi Wang, Yuan He, Hongxia Dan, Jiantang Yang, Hui Wang, Dongjuan Liu, Hui Feng, Kai Jiao, Qianming Chen
Journal: International Journal of Oral Science (2022)

Abstract The complexity of oral ulcerations poses considerable diagnostic and therapeutic challenges to oral specialists. The expert consensus was conducted to summarize the diagnostic work-up for difficult and complicated oral ulcers, based on factors such as detailed clinical medical history inquiry, histopathological examination, and ulceration-related systemic diseases screening. Not only it can provide a standardized procedure of oral ulceration, but also it can improve the diagnostic efficiency, in order to avoid misdiagnosis and missed diagnosis.
Adenoma Detection Rate and Colorectal Cancer Prevention by Colonoscopy
Authors: Douglas K. Rex
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
LGG-44. Multi-omic analysis reveals integrated signalling networks in paediatric low-grade glioma
Authors: Lewis Woodward, Tania A Jones, Ankit Patel, Arran D Dokal, Thomas J Stone, Vinothini Rajeeve, Pedro R Cutillas, David T W Jones, Darren Hargrave, Thomas S Jacques, Denise Sheer
Journal: Neuro-Oncology (2022)

Abstract Paediatric low-grade gliomas (pLGGs) are the most common type of childhood CNS tumours. Our study included pilocytic astrocytomas (PAs; KIAA1549:BRAF), glioneuronal tumours (GNTs; BRAFV600E) and location-matched controls. We initially performed kinase substrate enrichment analysis (KSEA) to infer differential kinase activity, which allowed us to identify altered signalling networks in the two tumour types. Here we report the integration of these kinase signalling networks together with total proteomics, transcription factor enrichment analysis (TFEA) and transcriptomics (coding and non-coding). Total proteomic profiling confirmed an increase in proteins involved in cell cycle, inflammatory response and signal transduction in PAs, whilst there was an increase in proteins promoting cell growth, immune response and inflammation in GNTs. TFEA was performed using the DoRothEA database to identify master transcriptional regulators. We observed signiﬁcant activation of transcription factors (TFs) that are direct targets of MAPK signalling in both tumour types. Notable differences include the higher activation of NF-kB/STAT TFs in PAs and the increased activation of RFX1/2 in GNTs. Next, we constructed kinase-TF networks and identified multiple kinases targeting STAT3 in PAs and STAT1/3 in GNTs. Pathway analysis of RNA-Sequencing data showed enrichment of NF-kB in both tumours and repression of E2F target genes (PA) and reduced expression of MYC target genes (GNT). We developed a BRAF-OIS signature and found 23 genes commonly enriched in both tumour types, highlighting shared senescence-associated targets. MicroRNA profiling identified upregulation of microRNAs that target MAPK and NF-kB signalling networks, and many down-regulated microRNAs with tumour suppressive roles. Finally, we identified several lncRNAs known to be differentially expressed in glioma and, whilst their mechanism(s) of action are varied, they are thought to act with other well-established regulators to fine-tune cellular processes. Taken together, we present a comprehensive signalling network as a framework for studying pLGGs.
EPEN-16. Epithelial Progenitor Cell Abundance and Copy Number Variant Gains and Losses Impact the Biology of Recurrent Ependymoma
Authors: Gregory Norris, Rui Fu, Kent Riemondy, Nicholas Willard, Andrea Griesinger, Vladamir Amani, Enrique Grimaldi, Faith Harris, Ahmed Gilani, Todd Hankinson, Jay Hesselberth, Nicholas Foreman, Andrew Donson
Journal: Neuro-Oncology (2022)

Abstract Ependymoma (EPN) is a common pediatric brain tumor that is fatal in approximately 50% of cases. Posterior fossa A (PFA) EPN has the highest rate of recurrence and the worst prognosis of all EPN subtypes. At relapse, it is typically incurable even with re-resection and re-irradiation. The biology of recurrent ependymoma remains largely unknown, which hinders clinical advances. In this study, we use paired samples of primary and recurrent disease from the same patient to investigate the drivers of recurrence. DNA methylation studies reveal frequent copy number variants at recurrence that were not present at primary presentation. We report a frequent gain of chromosome 1q and loss of 6p at recurrence, which has not been previously reported and may be a driver of recurrent disease. We have previously shown that PFA EPN is comprised of 4 main neoplastic cell populations, two well-differentiated populations termed ciliated and transportive ependymal cells, a mesenchymal cell population, and an undifferentiated population. Using spatial transcriptomics (Visium) integrated with single-nuclei RNA-seq (Chromium), we discovered that a highly proliferative EPN progenitor population of epithelial lineage is significantly upregulated at recurrence which we hypothesize drives refractory disease. Accordingly, we found higher expression of EPN progenitor gene signatures in bulk RNA transcriptomes of primary tumors that later recurred compared to tumors that never recurred. Together, these findings highlight the biologic differences between primary and recurrent disease and add to our understanding of treatment resistance in childhood ependymoma.
Breath biopsy early detection of lung cancer using an EVOC probe targeting tumor-specific extracellular β-glucuronidase.
Authors: Christiaan Frederick Labuschagne, Rob Smith, Neelam Kumar, Max Allsworth, Billy Boyle, Sam Janes, Phil Crosbie, Robert Rintoul
Journal: Journal of Clinical Oncology (2022)

2569 Background: Lung cancer is a leading cause of mortality with 5-year survival less than 20%, largely a result of many cases being diagnosed late. Early detection can increase cancer survival up to 13-fold underscoring the need for effective screening. Targeted Low dose computed tomography (LDCT) has been shown to be effective but its impact to date has been limited due to slow adoption and variable uptake in high-risk populations. Breath analysis represents a non-invasive screening approach either alone or alongside LDCT. Numerous studies have investigated potential endogenous breath biomarkers of lung cancer. Many have produced promising results but to date, no validated biomarkers with clear connections to cancer metabolism have been revealed. We have explored an alternative, probe-based approach based around Exogenous Volatile Organic Compound Probes (EVOC Probes). The probes target tumour associated extracellular b-glucuronidase, a glycosidase enzyme that normally resides within lysosomes. Methods: We use a hydrophilic non cell permeable substrate probe D5-ethyl-βD-glucuronide (D5-EtGlu) that upon hydrolysis by the target enzyme releases D5-ethanol, a unique volatile reporter molecule detectable on breath. This provides a readout of tumour associated enzyme activity using breath analysis. Results: Administering D5-EtGlu to mice resulted in tumour specific release of D5-ethanol, enabling discrimination between healthy and tumour bearing animals. Increased expression of b-glucuronidase in lung cancer tissue and the tumour microenvironment was confirmed with immunohistochemistry (IHC) in clinical samples. A phase 1a clinical trial administered D5-EtGlu to healthy individuals in a single ascending dose study to establish safety and background D5-ethanol levels in healthy individuals. This resulted in no adverse events and low/no D5-ethanol signal verifying the inaccessibility of D5-EtGlu to intracellular b-glucuronidase. The next stage, currently ongoing, is a proof of mechanism in humans. D5-EtGlu is administered intravenously to confirmed lung cancer patients followed by breath analysis. D5-ethanol breath levels will be compared to cancer free individuals receiving the same dose of D5-EtGlu. Conclusions: Non-invasive breath testing has great potential to contribute to diagnosis for lung cancer including a potential role in screening. Our current work is evaluating the use of an administered probe to stimulate tumour-specific enzyme activity and produce a marker detectable on breath. Continued success could result in a sensitive and highly specific method for lung cancer early detection.
Regorafenib in refractory metastatic colorectal cancer: A multi-center retrospective study.
Authors: Donghao Xu, Yu Liu, Wentao Tang, Lingsha Xu, Tianyu Liu, Jisheng LI, Jiemin Zhao, Le-chi Ye, Jianmin Xu, Wenju Chang
Journal: Journal of Clinical Oncology (2022)

e15580 Background: Regorafenib improves progression-free survival (PFS) and overall survival (OS) in patients with refractory metastatic colorectal cancer (mCRC). Here, we report the treatment patterns of regorafenib in the third- or late-line setting for mCRC in four centers in China. Methods: Patients with refractory mCRC in four centers in China administered regorafenib from February 1, 2018 to June 31, 2021 were enrolled. Patients were grouped into 3 cohorts, including the monotherapy (regorafenib alone), chemo (regorafenib plus chemotherapy) and immune (regorafenib plus anti-PD1 (programmed cell death 1) antibodies) groups. Demographic, clinical, survival and safety data were retrospectively analyzed. Results: A total of 177 patients were included in this study. Of them, 116 (65.5%) were treated with regorafenib alone, while 28 (15.9%) and 33 (18.6%) were administered regorafenib plus chemotherapy and anti-PD1 antibodies, respectively. The median followedup time was 9.2 months. The disease control rate (DCR) was 40.7%. The median PFS (mPFS) was 2.43 months and the median OS (mOS) was 12.2 months. The immune group had longer median PFS (3.5 m vs. 2.2 m, p = 0.043) compared with the monotherapy group. Patients administered regorafenib plus chemotherapy had longer median OS (15.9 m vs. 8.4 m, p = 0.032) compared with the monotherapy group. Patients who began regorafenib treatment at 120 mg had longer median PFS and OS compared with those who began at 80 mg (PFS: 3.7 m vs. 2.0 m; p &lt; 0.001; OS: 13.4 m vs. 10.2 m; p = 0.005). Patients with a final dose of 120 mg had longer median PFS and OS compared with the 80 mg or less group (PFS: 5.0 m vs. 2.3 m; p = 0.045; OS: UR (unreach) vs. 10.9 m; p = 0.003). There were 87.0% (154/177) patients experience AEs. Three groups had similar rates of AEs (86.2% vs. 89.3% vs. 87.9%; p = 0.89). Conclusions: Patients administered regorafenib alone or regorafenib in combination with other agents were relieved to some extent, with a disease control rate of 40.7%. Regorafenib plus anti-PD1 antibodies showed better PFS, while regorafenib plus chemotherapy had the most benefit in OS. There was no significant difference among three groups in terms of AEs.